Experimental and numerical characterization of a grounded coplanar waveguide for nanoelectroporation applied to liposomes

AbstractElectroporation has become a powerful technological platform for the electromanipulation of cells and tissues for various medical and biotechnological applications. Recently, nanoporation based on nanosecond pulsed electric fields (nsPEFs) has gained great attention due to its potential to permeabilize the membrane of small vesicles. Here, the authors propose and characterize, both experimentally and through multiphysics modeling, a grounded coplanar waveguide compliant with the wideband requirements for nanosecond pulses to be used for experiments of drug delivery with liposomes activated by nsPEFs

Electric Field Bridging-Effect in Electrified Microfibrils’ Scaffolds

Introduction: The use of biocompatible scaffolds combined with the implantation of neural stem cells, is increasingly being investigated to promote the regeneration of damaged neural tissue, for instance, after a Spinal Cord Injury (SCI). In particular, aligned Polylactic Acid (PLA) microfibrils’ scaffolds are capable of supporting cells, promoting their survival and guiding their differentiation in neural lineage to repair the lesion. Despite its biocompatible nature, PLA is an electrically insulating material and thus it could be detrimental for increasingly common scaffolds’ electric functionalization, aimed at accelerating the cellular processes. In this context, the European RISEUP project aims to combine high intense microseconds pulses and DC stimulation with neurogenesis, supported by a PLA microfibrils’ scaffold. Methods: In this paper a numerical study on the effect of microfibrils’ scaffolds on the E-field distribution, in planar interdigitated electrodes, is presented. Realistic microfibrils’ 3D CAD models have been built to carry out a numerical dosimetry study, through Comsol Multiphysics software. Results: Under a voltage of 10 V, microfibrils redistribute the E-field values focalizing the field streamlines in the spaces between the fibers, allowing the field to pass and reach maximum values up to 100 kV/m and values comparable with the bare electrodes’ device (without fibers). Discussion: Globally the median E-field inside the scaffolded electrodes is the 90% of the nominal field, allowing an adequate cells’ exposure

Electroporation mechanisms: The role of lipid orientation in the kinetics of pore formation

Electroporation is a well-established technique used to stimulate cells, enhancing membrane permeability. Although the biological phenomena occurring after the poration process have been widely studied, the physical mechanisms of pore formation are not clearly understood. In this work we investigated by means of molecular dynamics simulations the kinetics of pore formation, linking the different stages of poration to specific arrangements of lipid membrane domains.Clinical Relevance-The approach followed in this study aims to shed light on the molecular mechanisms at the basis of the electroporation technique, nowadays used to enhance the entrance of poorly permeant anticancer drugs into tumor cells, for gene electrotransfer and all the other applications exploiting the modulation of cell membrane properties

A coplanar waveguide system for drug delivery mediated by nanoelectroporation: an experimental and numerical study

Nanosecond pulsed electric fields (nsPEFs) can interact with lipid vesicles, that are primary drug delivery nanocarriers activated by external signals. In this work, authors propose a new setup of an experimental bench suitable for nsPEFs exposure of liposome nanosystems, compliant with the wideband requirements for nanosecond pulses. A multiphysics modelling able to predict liposome poration is proposed to define the characteristics of signals to be used in experiments

Response of Hydrated Lipid Bilayers to RF EM Fields: Molecular Dynamics Investigations

Molecular dynamics (MD) simulations give the chance to evaluate physical interactions in biological matter occurring at the atomistic level and in nanosecond or microsecond timescales. Due to the ongoing interest in using radiofrequency (RF) electromagnetic (EM) fields both for a wide range of biomedical applications and for the interaction mechanisms at the basis of health effects, a deep investigation on their effects to biological membrane is needed.In this work the response of a biological hydrated membrane to the application of RF EM fields was studied from an atomistic point of view, comparing the effects with the ones induced by a static field exposure

Microdosimetry in a realistic keratinocyte cell model at mmWave and HF frequencies

International audienceWide spread of millimeter-wave (mmWave) and wireless power transfer (WPT) technologies opens new challenges in terms of characterization of bioelectromagnetic interactions. The objective of this study is to investigate quantitatively the induction of such electromagnetic radiation within cells at 6.78 MHz and 60 GHz respectively. A realistic model of the keratinocyte, which takes into account the complex morphologies and volume fraction of organelles, was developed. The finite element method ( FEM) was used to solve the Laplace's equation under quasi-static approximation. The results show that the power loss density (PLD) within the cellular and subcellular compartments increases with frequency due to diminished shielding effect of the membranes. At 60 GHz and 6.78 MHz, the average power loss density (PLDavg) within the cellular and subcellular organelles is about six and three orders of magnitude higher than that at 1 kHz. Also, in comparison to the background PLDavg within cytoplasm (CP), the intracellular traffic through the nuclear pores (N-p) is submitted to three orders of magnitude higher exposure level at 6.78 MHz and 2.5 times higher exposure level at 60 GHz

Galvanotactic phenomenon induced by non-contact electrostatic field: Investigation in a scratch assay

Non-contact galvanotaxis as a way to drive the cells migration could be a promising tool for a variety of biomedical applications, such as wound healing control, avoiding the interaction between electrodes and cell cultures. To this regard, the efficacy of this electrical stimulus application has to be deeper studied to control physiological migratory phenomena in a remote way.Aim of this work is to provide an experimental investigation on the mobility of cells exposed to a static electric field in a "noncontact" mode, supported by a suitable modeling of the electric field distribution inside the experimental setup. In particular, scratch assays have been carried out placing the electrodes outside the cells medium support and changing the cells holder to study more than one configuration.Clinical Relevance— In this study the in vitro experiments on the non-contact galvanotaxis, together with the numerical simulations of the exposure setup, provide a way to investigate the effects that could affect an electrically drive cell migration